Factors Associated With COVID-19 Vaccine Response in Transplant Recipients: A Systematic Review and Meta-analysis

Abstract

Background: The rapid development and universal access to vaccines represent a milestone in combating the coronavirus disease 2019 (COVID-19) pandemic. However, there are major concerns about vaccine response in immunocompromised populations in particular transplant recipients. In the present study, we aim to comprehensively assess the humoral response to COVID-19 vaccination in both orthotopic organ transplant and allogeneic hematopoietic stem cell transplant recipients.

Methods: We performed a systematic review and meta-analysis of 96 studies that met inclusion criteria.

Results: The pooled rates of seroconversion were 49% (95% confidence interval [CI], 43%-55%) in transplant recipients and 99% (95% CI, 99%-99%) in healthy controls after the second dose of vaccine. The pooled rate was 56% (95% CI, 49%-63%) in transplant recipients after the third dose. Immunosuppressive medication is the most prominent risk factor associated with seroconversion failure, but different immunosuppressive regimens are associated with differential outcomes in this respect. Calcineurin inhibitors, steroids, or mycophenolate mofetil/mycophenolic acid are associated with an increased risk of seroconversion failure, whereas azathioprine or mammalian target of rapamycin inhibitors do not. Advanced age, short interval from receiving the vaccine to the time of transplantation, or comorbidities confers a higher risk for seroconversion failure.

Conclusions: Transplant recipients compared with the general population have much lower rates of seroconversion upon receiving COVID-19 vaccines. Immunosuppressants are the most prominent factors associated with seroconversion, although different types may have differential effects.

FIGURE 1.

Flowchart of studies screening and selection process. COVID-19, coronavirus disease 2019.

FIGURE 2.

Comparing the rates of humoral response to COVID-19 vaccines between transplant recipients and healthy controls. Weights and between-subgroup heterogeneity test are from random-effects model; continuity correction applied to studies with zero cells. allo-HSCT, allogeneic hematopoietic stem cell transplantation; CI, confidence interval; COVID-19, coronavirus disease 2019; DL, DerSimonian-Laird; SOT, solid organ transplantation.

FIGURE 3.

Risk factors of failure in humoral response to COVID-19 vaccines in transplant recipients. (A) Dichotomous data; (B) Continuous data. ^#Only studies describing allo-HSCT populations. BMI, body mass index; CI, confidence interval; COVID-19, coronavirus disease 2019; eGFR, estimate glomerular filtration rate; GVHD, graft vs host disease; mTOR, mammalian target of rapamycin; WMD, weighted mean difference.